Bibliometric and visual analyses of research on the links between stroke and exosomes from 2008 to 2023

Exosomes, which are extracellular vesicles secreted and released from specific cells, exist widely in cell culture supernatants and various body fluids. This study aimed to analyze the research status of exosomes in stroke, and predict developmental trends via bibliometric analyses. The related literature from January 1, 2008 to January 1, 2024 was searched in the Web of Science Core Collection and 943 articles were retrieved. VOSviewer was used to visualize national cooperation and institutional cooperation. Cluster analysis of keywords and Citespace were applied for mutation analysis. Results: The analysis of 943 works of literature showed that the number of published articles has been steadily increasing since 2015. It is predicted that nearly 211 articles will be published in 2024 and 220 annually by 2028. China has the largest number of publications (473), followed by the United States (234), and Germany (61). The institution with the most publications is Henry Ford Hospital (Detroit, MI). In the keyword cluster “Exosomes and the Mechanism of Stroke: Inflammation and Apoptosis,” exosomes and inflammation were identified as hotspots. “Functional recovery” was a new trend in the keyword cluster of “Angiogenesis and Functional Recovery after Stroke.” China and the United States are the main forces in this field, and both countries focusing on drug treatments. The studies have been published mainly in China and United States. The findings of our bibliometric analyses of the literature may enable researchers to choose appropriate institutions, collaborators, and journals.


Introduction
Stroke includes ischemic stroke and hemorrhagic stroke [1] and the high probability of disability and death is associated with.One quarter of strokes are recurrent. [2]According to statistics, 1 person dies of a stroke every 3.5 minutes in the United States. [3]troke is the leading cause of death and long-term disability in middle-aged and elderly people in China.In 2019, there were 3.94 million new cases of stroke in China, which directly resulted in 2.19 million deaths. [4]nfortunately, despite the very high incidence of stroke and other cerebrovascular diseases, there is still a lack of effective treatments.[7] Presently, the treatment of ischemic stroke is limited to thrombectomy and the administration of tissue plasminogen activator (tPA), [8] but these 2 methods have a narrow time window in which they are effective.Less than 10% of patients with stroke benefit from tPA treatment [9] Intracerebral hemorrhage can be a complication of tPA administration, and it too is in urgent need of more effective treatment. [10]he exosome is a type of biomarker and carrier of intercellular biological information. [11]Exosomes can be used as carriers to deliver stroke drugs for repairing internal nerves and promoting angiogenesis. [12]In addition, exosomes secreted by

This research was funded by Natural Science Foundation of Zhejiang Province [No. LY22H270002], Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project [2023ZR011], China Postdoctoral Science Foundation [2023TQ0295], Postdoctoral research projects merit-based funding in Zhejiang province (First-class funding) [ZJ2023021], National Natural Science Foundation of China [No. 81904083], Zhejiang Basic Public Welfare Research Project [No. LGN19C190004], Zhejiang University Students Science and Technology Innovation Activity Plan & New Seedling Talent Plan [No. 2022R410A032].
the mesenchymal stem cell (MSC) are related to inflammation regulation and neuroprotection.MSC-derived mixtures of exosome host proteins and RNAs have been identified, some of which are involved in anti-inflammatory, antigen presentation, or neuronal protection pathways. [13,14]Furthermore, exosome microRNA plays a role in cerebral ischemia by promoting cell communication, regulating the nervous system, reshaping the blood vessels, and inhibiting neuroinflammation. [15,16]ibliometrics is a systematic and effective method for analyzing the scientific literature.Although this method has been applied to the subject of stroke, a bibliometric analysis that focuses specifically on the role of exosomes in stroke was needed to evaluate the current status of research in this field.In our study, bibliometrics was used to explore research directions and hotspots, as well as to predict publication trends.Similarities as well as differences in the number of publications, research directions, and cooperation between China and the United States were determined.This study aimed to elucidate the complete scenario in this field and provide a novel perspective for researchers.

Materials and methods
The data were obtained from the Web of Science (WoS), a database of scientific literature maintained by Clarivate Plc (London, UK).The database is a high-quality academic collection [17] that provides its reference number, which is conducive to qualitative and quantitative analyses.The authors obtained the initial data from the WoS Core Collection (WoSCC).The language was set to English, and the literature type was selected as "article or review."The search covered January 1, 2008 through January 1, 2024.All documents were retrieved on January 1, 2024 to avoid any bias due to the daily updates in the database.

Mathematical model and prediction
Based on the data obtained for from 2008 to 2023, a mathematical model was used to perform nonlinear regression.As the annual publication volume was predicted, we estimated that it would increase every year at a certain rate, albeit it would not exceed a threshold.Therefore, we established a logistic growth model where N is the number of publications and t is the year of publication, according to the equation shown in Figure 1A.

Data analyses
The "Journal Citation Reports" (JCR) of the WoS were applied to evaluate the impact factor (IF) of journals.The "Essential Science Indicators" of the WoS was also used to evaluate the ranking of institutions.The data obtained from WoSCC were downloaded and imported into Excel, Bibliometric Online Analysis Platform (https://bibliometric.com),VOSviewer 1.6.18(Centre for Science and Technology Studies, Leiden University, Leiden, Netherlands), and CiteSpace 6.2.R7 (https://citespace.podia.com/download).Excel was used to analyze the data of time and publication volume, and a model was established to predict the publication volume.Bibliometric Online Analysis Platform was applied to visualize the annual publication volume of different countries.VOSviewer was used to analyze the national and institutional cooperation and to visualize keywords.CiteSpace was applied to analyze the mutations of Chinese and American subject categories and the mutations of Chinese, American, and global keywords.

Annual publications
Our search of WoSCC covered January 1, 2008 through January 1, 2024 and retrieved a total of 943 articles.From 2008 to 2012 (except 2009), 2 articles were published every year (Fig. 1A).From 2013 to 2023, the overall annual publication volume increased year-by-year.Furthermore, 2013 was probably a turning point because Hongqi Therefore, the research field of exosomes in stroke has gradually become a hotspot.We have predicted and analyzed its annual publication volume.The obtained prediction curve and existing data as of January 1, 2024 are shown in Figure 1A.By fitting the established model, the relationship between time and annual publication volume was obtained.The goodness of fit (R²) was 0.993, which indicates a very high degree of fitting According to our model, it is predicted that nearly 211 relevant articles will be published in 2024.Looking further ahead, it is expected that 220 papers will be published annually by 2028.

Publishing countries and regions
Articles about "exosome in stroke" have been published in 60 countries.Combined with the cited times, it can be seen that the United States contributed immensely to this research during 2012 to 2013, which led to the rise of this field.As of January 1, 2024, the top 3 countries for the total number of published articles were China (N = 473), the United States (N = 234), and Germany (N = 61).
We selected the top 2 countries, China and the United States, for further comparative analysis.
Since 2015, the annual number of publications in both countries has increased year-by-year (Fig. 1B).Interestingly, in terms of time span, the United States was the country to start the research earlier (2008) than China (2010) and contribute to the rise of the field.However, in terms of quantity, China has more publications than the United States (473 vs 234).
From the perspective of research direction, in China and the United States, CiteSpace was used to analyze the mutation of the WoS discipline (subject) category.The top 5 subject categories with the strongest citation bursts in China are shown in Figure 2A.The top 20 subject categories with the strongest citation bursts in the United States are shown in Figure 2B.The latest and highest mutation intensity of the subject category in China is "Medicine, Research, & Experimental" during 2019 to 2020.The latest and very strong category mutations in the United States are "Chemistry," and "Materials Science" and "Nanoscience & Nanotechnology" for the period 2020 to 2022.These findings illustrate the latest changes in the research directions of the 2 countries.
National cooperation in this research area was analyzed by VOSviewer (Fig. 3).China and the United States are the 2 most active countries in this field, and these 2 countries exhibit the highest cooperation (green circles).The total link strength of the United States is 65,039 and that of China is 73,376.Germany ranks third (yellow circle), with a total connection strength of 31,975.The link strength between China and the United States is 27,854, which is the closest cooperative relationship.Meanwhile, the intensity of cooperation between China and Germany ranks second (9355).In contrast, the connection strength of other countries is far less than this value, which is relatively not close.
From the perspective of national cooperation, it is not difficult to see that the close cooperative relationship between the United States and China (Fig. 3, thick green line) may be the reason for the similarities in their research directions.Both the total link strength and publication volume of Germany and the United Kingdom are lower than those of China and the United States, possibly because China and the United States are better at managing cooperative relations.

Citation frequencies
The citation frequency can reflect the influence of an article on a research field.The top 10 most-cited research papers (articles) about "exosomes in stroke" are shown in Table 1, with the top co-cited by many other papers.Table 3 lists the top 10 co-cited works of literature cited in this field, including their first authors and journals.The paper "Systemic Administration of Exosomes Released from Mesenchymal Stromal Cells Promote Functional Recovery and Neurovascular Plasticity after Stroke in Rats" (2013) is the most frequently co-cited paper, with a total of 217 times.The first author of this paper is Hongqi Xin.From Table 3, it is evident that Hongqi Xin as a first author appears repeatedly in the top 10 co-cited papers, appearing in a total of 4 papers (36.3%).This is not a common situation, which indicates that the author has extensive influence on the research basis in this field.
We used Citespace to analyze the co-cited references.The 943 articles retrieved from WoSCC were divided into 96 clusters.The largest 20 clusters are shown Figure 4, arranged vertically according to cluster size.The timeline is shown horizontally.The original cluster at the top of the figure is the latest cluster with high reference or reference mutation, but probably due to the wide range of research and cooperation in recent years, many clusters cannot extract features well.This reflects the consistency of research in this field from the side, perhaps indicating that there is no new mutation, but continues to dig into the original research.To gain a clearer insight into how they are grouped together, we included the tag content in Table S3, Supplemental Digital Content, http://links.lww.com/MD/N477.The clarity of keyword clustering results was judged by module value (Q-value) and average contour value (S-value).When Q > 0.3, the clustering structure is significant.When S > 0.5, the clustering result is reasonable; when ≥ 0.7, the clustering is highly efficient. [19]The Q value of this cluster is 0.6254 and its S value is 0.86, which is clear and efficient.

Published journals
Articles examining the role of exosomes in stroke have been published in 372 journals.The top 10 active journals are listed in Table 4. From the total number of articles, it is clear that International Journal of Molecular Sciences is the largest contributor to the field, followed by Stem Cell Research & Therapy.The JCR partitions of these journals are in Q1 (58.8%) and Q2 (41.2%), which implies that this literature is innovative to a certain extent and that the published studies are relative

Institutional cooperation
A total of 1267 institutions have published articles in this field.Henry Ford Health System was the most prolific institution, with 49 publications, followed by Henry Ford Hospital, one of its constituent units, with 48.Oakland University (Rochester, MI; <30 miles from Henry Ford Hospital) is third with 39 publications.The top 10 organizations with the highest number of publications are shown in Table 5.There are 5 organizations in the United States, 6 in China, and 2 in Germany.
We used VOSviewer to visualize the cooperation between institutions (Fig. 5).While 92 institutions are above the threshold of the minimum number of published articles (N = 5), and they exhibit cooperation.There are 1129 institutions that are below the threshold of 5 published articles, and they exhibit less cooperation with other organizations.
Moreover, the link strength of most institutions is not very high, implying that cooperation between institutions is concentrated in certain institutions (Table S1, Supplemental Digital Content, http://links.lww.com/MD/N477).The total link strength of Henry Ford Hospital is second (35,990), despite having with the highest number of articles (N = 49), and that of Oakland University is first (39,873), but with the third-highest number of posts (N = 39).

Co-occurrence of keywords
According to established search principles, keywords were selected that reflect the overall focus of the research. [20]OSviewer was used for keyword analysis (Fig. 6).Keywords were divided into 5 clusters: red, green, blue, yellow, and purple.The red cluster named "Exosomes and the Mechanism of Stroke: Inflammation and Apoptosis."was the largest keyword cluster and has the main keywords of extracellular vesicles, inflammation, microrna, and biomarkers.The yellow cluster was titled "Brain Injury and Neurorepair," with main keywords of exosomes, brain, ischemic stroke, and neurogenesis.The blue cluster was named "Angiogenesis and Functional Recovery after Stroke," with main keywords of stroke, functional recovery, stem cells, and transplantation.The yellow cluster was titled "Treatment Strategies for Stroke," and its main keywords are cerebral-ischemia, blood-brain-barrier, and in vitro.The purple cluster was titled "Associated nerve damage," and its main keywords are neuroinflammation, alzheimers-disease, and spinal-cord-injury.
The criterion of at least 10 occurrences of all keywords was chosen, and 190 keywords met this criterion.The top 5 keywords were "extracellular vesicles," "exosomes," "stroke," "functional recovery," and "ischemic stroke."It is worth noting that, aside from the topic-related keywords, "stromal cells" ranks 8th (Table S2, Supplemental Digital Content, http://links.lww.com/MD/N477).Taken together, these results should help researchers to check the hot spots in the field of stroke, and turn to the research of stroke recovery, exosome treatment and stem cell therapy.
CiteSpace was used for the timeline analysis of keywords.Keywords were divided into 12 clusters (Fig. 7).To gain a clearer insight into how they are grouped together, we included the tag content in Table S4, Supplemental Digital Content, http://links.lww.com/MD/N477.These clusters were different from those in the VOSviewer analysis to some extent, but we could see that there were similarities for the keywords of stem cells and extracellular vesicles.The top keyword cluster was extracellular vesicle.The value of Q is 0.3969 and the value of S is 0.7259, which indicates that this cluster is relatively stable.From the timeline analysis, brain-heart interaction, mesenchymal stem cells, blood-brain barrier integrity and stem cell therapy are all relatively new keyword clusters, while blood-brain barrier integrity is a cluster with a longer duration.
Moreover, the mutation of keywords can reflect the sudden change in the citation frequency of keywords at a certain time and lock the frontier of this field for us.CiteSpace was employed to analyze the keyword mutations.Because the number of published articles is relatively small, the mutation intensity is small.The top 15 keywords with the strongest citation bursts are shown in Figure 8.The highest mutation intensity was 4.38 for Alzheimer disease and the time range of mutation was from 2014 to 2016.The most recent mutation, pathway, had an intensity of 3.34, with time range of mutation from 2022 to 2024.From the analysis of keywords, "stromal cells" appeared most frequently in both China and the United States.Using CiteSpace, the mutations of Chinese and American keywords were obtained using the same method.The keyword with the highest mutation intensity in China was "mesenchymal stromal cell" (strength = 5.39), with the mutation period of 2017 to 2020 (Fig. 9A).The keyword with the highest mutation intensity in the United States was "neurovascular plasticity" (strength = 3.44), with the mutation period of 2016 to 2019 (Fig. 9B).
Authorship There were a total of 4850 authors who had published articles about exosomes in stroke.The top 10 authors with the highest number of publications are listed in Table 6.Michael Chopp of the United States has the highest number of publications (N = 39) and citations (N = 4738).Thorsten R Doeppner of the Germany ranks second, with 21 articles and 1156 citations.Guoyuan Yang, Zhijun Zhang and Yaohui Tang are emerging authors in this field, as their average publication year is 2021 and beyond, and their numbers of publications are ranked in the top 10.Most of the top 10 prolific authors are based in the United States (N = 3) or Germany (N = 4), with 3 authors from China.Given that authors in China publish the largest total number of articles in the world, a possible reason there is only 3 authors in China in the top 10 prolific authors is because there are more authors in the country.This finding indicates that research in this field in China has become a hotspot, but it needs to be further deepened.

Discussion
This study focuses on the field of "role of exosomes in stroke" using bibliometrics for the first time.We describe the status quo of articles published in this field since the emergence of research, and provide a comparative analysis of China and the United States.
In this study, 943 articles were included and publication trends were predicted.According to our logistic model, 220 articles are expected to be published in 2028.China and the United States are the 2 countries with the highest number of publications, their cooperation in this field is the closest in the world, and their influence on this field is far-reaching.
Both Chinese and American studies focus on Neurosciences, Neurology, and Cell Biology.However, China's recent move to the category of Medicine, Research, & Experimental indicates that research is focused on exosomal delivery as a treatment for stroke.Moreover, targeted delivery of exosome miR-124 has been shown to play a key role in neuroprotection during cerebral ischemia. [15,21]The shift in the United States to "Chemistry" and "Materials Science" is actually studying exosomes as drug delivery carriers for treating brain injuries. [22,23]nterestingly, although there is more literature published by China, the intensity and number of citation mutations in discipline direction are not as strong as in the United States, which may reflect the greater proficiency in disciplines in the field in the United States.At the same time, Germany also occupies a place in this field, its cooperation intensity is in the third place, and its authors are more active.The total number of articles published in China, the United States and Germany accounts for most of the research literature (81.68%).This indicates that the research is relatively scattered among other countries, and we speculate that this is because the cooperation intensity of other countries is relatively low and the cooperation is not extensive enough.
According to our analysis, China, Henry Ford Hospital, and Michael Chopp are the country, institution, and author with the highest number of publications in this field.Articles by American author Hongqi Xin not only accounted for 4 of the top 10 co-cited papers but also the top 2 most-cited papers.The author has led the research in this field and was a cornerstone of its emergence.
The research in terms of countries or regions and their cooperation reveals the global attitude and the current situation of research.In general, the cooperation is not close enough.From the regional point of view, Europe is the region with the most cooperation with other continents, as its cooperation intensity is the largest.Asia has the highest number of publications, and its cooperation intensity is obvious.This may be because China has great influence in this field.
Journal analysis provides guidance for choosing suitable journals in which to publish research.In general, the JCR partition and IF of the journals that publish articles about exosomes in stroke are considerable, which indicates that the research in this field is at the forefront.Interestingly, International Journal of Molecular Sciences in Q1 was the most active, but its citations per papers count was less prominent than that of other Q1 journals.The possible reason is that it is a relatively new journal as far as publication of articles this field.Relevant articles were last published in Stroke in January 2017, which is close to the earliest publication time of this journal.Thus, time difference for the last publication in Stroke versus International Journal of Molecular Sciences is large.Hence, Stroke is more well-known and has an advantage in citation times.
Among the institutions, Henry Ford Hospital is the most active one, probably because the top 2 active authors Michael Chopp and Zheng Gang Zhang, and the important author Hongqi Xin work there.However, the institution is not as cooperative as Oakland University, the third most active university.Southeast university (Nanjing, Jiangsu, China) was in the top 5 cooperative institutions but with relatively few articles.The Essential Science Indicators ranking shows that active institutions are more fragmented, which may be due to the choice of disciplines or not being closely related to the field.
Cluster analysis of keywords can provide a new angle for systematically studying the hotspots. [24]The cluster analysis of keywords included 5 clusters."Exosomes and the Mechanism of Stroke: Inflammation and Apoptosis" was the largest cluster, which indicates that exosomes are related to the internal mechanism of stroke, and there are many studies.Exosomes, as the communication media in cells, are composed of lipid bilayer membrane structures and carry RNA (mRNA, microRNA, and other noncoding RNA), DNA, protein, glycan, and lipid. [25]he exosomes were found to be related to the mechanism of stroke, which also manifested in many aspects.First of all, exosomes are secreted by many kinds of cells, and many kinds of MSC-derived exosomes have been shown to exhibit functional recovery and vascular repair, [26] which are conducive to alleviating cerebral ischemia-reperfusion injury.Secondly, microRNA in exosomes can play diversified roles, such as reducing neuroinflammation [27] and exerting neuroprotective effects [28,29] (Inflammation was one of the high-frequency keywords in this cluster.)According to the analysis of the keyword timeline, the future research direction may still focus on MSCs.
The mutation of keyword citation times can be used as a key indicator. [30]The keyword of the recent mutation is "circulating microRNA," which may be used as a diagnostic indicator because the level of some circulating exosomes (such as miRNA-223 and miRNA-17-5p) will increase after cerebral ischemia. [31,32]To some extent, this finding denotes the clinical significance of exosomes in cerebral ischemia.
By analyzing the mutations of keywords between China and the United States and global keywords, it could be seen that many global keyword mutations are caused by China and the United States.For example, "death" broke out in China in 2020 to 2021, whereas in the world, it broke out in 2020 to 2021."Neurovascular plasticity" broke out in the United States in 2016 to 2019, which corresponded to the world's outbreak Medicine Table 3 Top 10 co-citation of cited references.Two references were tied for 8th place, each with 104 citations frequency.Title Stem cell therapy is the focus of regenerative medicine research.Neural stem cell therapy was found to promote angiogenesis in rodents with positive effects on cerebral blood perfusion. [33]It seems to hold promise for the limited treatment options available for stroke, but the underlying mechanisms remain elusive. [34]tem cell transplantation can exert paracrine effects, and exosomes play an important role in paracrine effects. [35]The emergence of exosomes is a new possibility, and because of their low immunogenicity and targeting effect, the use of exosomes has become a new treatment option. [36]In our bibliometric analysis, although "cell therapy" appeared in the keyword and reference clustering, the co-occurrence and time intensity of "extracellular vesicles" were the largest.These findings confirm the leading role of cell therapy in exosome research.
There are many sources of exosomes, however, such as MSCs, tumor cells, and macrophages.In fact, research in this field cannot be done without exosomes secreted by MSCs.The MSCderived secretome contains a mixture of growth factors that promote tissue repair and regeneration and new angiogenesis.Studies have shown that MSC treatment can still significantly improve ischemic brain injury, independent of cell migration to the ischemic site. [37]In their review, Cunningham et al described the role of the MSC secretome in promoting repair in preclinical models of stroke as occurring through a variety of mechanisms including reduced neuroinflammation, neuroprotection, increased angiogenesis, and neurogenesis. [38]There is also growing interest in cell-free methods, such as exosomes or conditioned medium, which should be studied more comprehensively.The role of exosomes as delivery vehicles in ischemic stroke has been recognized.Researchers have used gold nanoparticles as markers for exosome neuroimaging in vivo, demonstrating the superiority of exosomes in treatment of various brain pathologies (including stroke, Alzheimer disease) and targeted drug delivery applications. [39]rom cell therapy to exosome therapy, a cell-free therapy, various research directions have been put forward.Exosomes mediate microRNA to promote the growth and repair of nerve cells. [21,40]In addition, the idea of using exosomes as clinical carriers for drug delivery has been widely recognized. [40,41]linically, the role of exosomes in stroke has been confirmed, but the mechanism is still under further study.
It can be seen from our bibliometric and visual analyses that the study of exosomes in stroke is necessary but still needs more in-depth investigation.Additional clinical trials are needed for confirmation.However, many researchers are optimistic about exosomes as a cell-free therapy, and the overall trend of exosome research is good.

Chinese medicine and exosomes
Exosomes, derived from various cell types with a size range from similar to 40 to 160 nm in diameter, have gained attention recently.Natural compounds are known to be one of the main constituents of traditional Chinese medicine (TCM). [42]xosomes can also be considered to ameliorate natural compounds, the main constituents of TCM, which are usually ignored due to the complexity of their structures, poor stability, and unclear mechanisms of action. [43]t the same time, Chinese medicine can alleviate the disease by treating exosomes.Shikonin, as a naphthoquinone isolated from the traditional Chinese medicine Lithospermum, can inhibit the proliferation of MCF-7 cells through reducing tumor-derived exosomal miR-128.And it suggests that shikonin suppresses MCF-7 growth by the inhibition of exosome release. [44]Danhong Injection and Danhong Injection-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in postinfarction myocardium. [45]s for ischemic stroke, research shows that Buyang Huanwu Decoction, a classic TCM decoction, is promising to alleviate neurological impairment after ischemic stroke.The mechanism is extracellular vesicles from medicated plasma of Buyang Huanwu decoction-preconditioned neural stem cells accelerate neurological recovery following ischemic stroke. [46] Chinese medicine and stroke

Gualou Guizhi decoction
Gualou Guizhi decoction (GLGZD), a well-established traditional Chinese medicinal formulation, is composed of 6 herbs, including Ramulus cinnamomi, Trichosanthis radix, Glycyrrhiza, Paeonia lactiflora, Zingiber officinale Roscoe, and Fructus jujubae, based on traditional Chinese medical theories "yin yang."Brain cerebral infarct size was also significantly decreased at day 7 following cerebral ischemia after treated with GLGZD.And GLGZD had a neuroprotective effect in ischemic brain injury, which was due to the inhibition of the inflammatory response and of NF-κB (p65) activation. [47]Studies have shown that GLGZD enhances the absorption and utilization of glucose by nerve cells after CI/R and exerts a significant antiinflammatory effect by regulating the polarization of microglia. [48]The findings of another study demonstrated that GLGZD facilitated neural function recovery through the promotion of cell proliferation, enhancement of axon regeneration, and augmentation in the population of neuronal precursors and  astrocytes within the peri-infarction region. [49]In conclusion, GLGZD can alleviate the damage caused by cerebral ischemia and produce anti-inflammatory and repair effects.

Huanglian-Jie-Du Decoction
Huanglian-Jie-Du Decoction (HLJDD), also known as Orengedoku-to in Japanese, is an important and classical multi-herb remedy in TCM.HLJDD is composed of Rhizoma coptidis, Radix scutellariae, Cortex phellodendri, and Fructus gardeniae at a ratio of 3:2:2:3.Studies have shown that active ingredients derived from HLJDD could protect against cerebral ischemia via anti-apoptosis effects.Baicalin can obviously reduce the nerve function defect and reduce the volume of cerebral infarction, and the neuroprotective effect of it partially due to myocardinrelated transcription factor-A-mediated transactivity, which might be controlled by the activation of phosphatidylinositol-3kinase and extracellular signal regulated kinase-1/2. [50]

Strengths and limitations
This study uses a scientific metrology analysis method to provide a more comprehensive and intuitive overview of the knowledge framework and research status of exosomes and stroke from 2008 to 2023.The study, however, is not without its limitations and deficiencies.55][56][57][58] Secondly, we did not include data from papers published in 2024 in our bibliometric analysis because the database is regularly updated and the dataset this year is not yet complete.Finally, some recently published high-quality studies may have been underestimated in our analysis due to limited frequency of citations.

Conclusion
Our study conducted bibliometric and visual analyses of the published articles on exosomes in stroke.These articles have been published mainly by China and the United States.Since 2013, the number of publications has increased year-by-year, indicating that this field has gained more attention.However, by 2021, the rate of growth in the field has slowed down, possibly because related research has reached a mature stage.Otherwise, overall international cooperation and institutional cooperation in this field need to be strengthened.There are similarities and differences in research between China and the United States, and these 2 countries cooperate closely.The recent research focus is on "circulating microRNA," whereas the research focus of China and the United States with the most published articles is "stem cells."Our study provides insights into the current status of stroke and exosome research, which may indicate its future trends.According to our keyword timeline analysis, the future research direction may still focus on exosomes derived from MSCs.Our study findings may enable researchers to select appropriate collaborative institutions, collaborators and journals for publication, as well as promote the in-depth study of exosomes in stroke.

Figure 2 .
Figure 2. Subject categories with the strongest citation bursts.(A) Top 5 in China.(B) Top 20 in the United States.

Figure 3 .
Figure 3. Analysis of national cooperation.
Systemic administration of exosomes released from mesenchymal stromal cells promote functional recoveryand neurovascular plasticity after stroke in rats cluster miR-17-92 cluster in exosomes enhance neuroplasticity and functional recovery after stroke in promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth of siRNA to the mouse brain by systemic injection of targeted www.md-journal.com in 2016 to 2018.The keyword "contributes" with the highest mutation intensity in the world was in 2018 to 2020, but the keyword mutation in China occurred in 2017 to 2020.One can speculate that global research on this degenerative disease might have influenced the research in China.

Figure 4 .
Figure 4. Timeline visualization of the reference co-citation map.

Figure 7 .
Figure 7. Timeline visualization of the keyword co-citation map.

Figure 8 .
Figure 8.The top 15 keywords with the strongest citation bursts.
Xin et al published their seminal article "Systemic Administration of Exosomes Released from Mesenchymal Stromal Cells Promote Functional Recovery and Neurovascular Plasticity after Stroke in Rats."As of January 1, 2024, this article had been cited 678 times and has led the research in this field.
IF = impact factor.
IF = impact factor.

Table 4
Top 10 journals with the largest number of publications.
IF = impact factor, JCR = Journal Citation Reports.

Table 5
Top 10 most-productive organizations.organizations were tied for 6th place, each with 23 articles.Two organizations were tied for 10th place, each with 17 articles.The institute's Essential Science Indicators (ESI) ranking is the ranking of the field of Neuroscience & Behavior.ESI = Essential Science Indicators. Three

Table 6
Top 10 active authors with the most numbers of documents.